Rutgeerts 2013.
| Methods | Randomised, placebo‐controlled, double‐blind within‐cohort study comparing etrolizumab to placebo (N = 48) | |
| Participants | Male and female adults (18‐70 years) with a diagnosis of UC for > 12 weeks and a Mayo Clinic Score (MCS) of > 5 points at screening | |
| Interventions | SAD stage (n = 25): 5 cohorts of patients received etrolizumab or placebo Cohort A: IV etrolizumab 0.3 mg/kg (n = 4) or placebo (n = 1) Cohort B: IV etrolizumab 1.0 mg/kg (n = 4) or placebo (n = 1) Cohort C: IV etrolizumab 3.0 mg/kg (n = 4) or placebo (n = 1) Cohort D: IV etrolizumab 10.0 mg/kg (n = 4) or placebo (n = 1) Cohort E: SC etrolizumab 3.0 mg/kg (n = 4) or placebo (n = 1) MD stage (n = 23): 5 cohorts of patients received etrolizumab or placebo Cohort F: SC etrolizumab 0.5 mg/kg (n = 4) Cohort G: SC etrolizumab 1.5 mg/kg (n = 5) Cohort H: SC etrolizumab 3.0 mg/kg (n = 4) Cohort I: IV etrolizumab 4.0 mg/kg (n = 5) placebo: (n = 5) |
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| Outcomes | Primary outcomes: adverse events, serious adverse events, dose limiting toxicity, maximum tolerated dose
Secondary outcomes: clinical response/remission at day 29 (SAD) and days 43 and 71 (MD); pharmacokinetic serum samples (etrolizumab concentration, maximum serum concentration, area under concentration–time curve from time 0 to infinity, area under concentration–time curve during a dosing interval, total body clearance at steady state after IV doses or apparent total body clearance at steady state after SC doses, elimination half‐life, antitherapeutic antibody response); pharmacodynamics evaluations (drug occupancy on target CD4+ lymphocytes; occupancy of etrolizumab; absolute number of T lymphocyte subsets) |
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| Notes | ||
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Conducted by an interactive voice response system based on a process designed by a biostatistician |
| Allocation concealment (selection bias) | Low risk | Conducted by an interactive voice response system based on a process designed by a biostatistician |
| Blinding of participants and personnel (performance bias) All outcomes | Unclear risk | double‐blind |
| Blinding of outcome assessment (detection bias) All outcomes | Unclear risk | Not described |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | Withdrawals were similar across groups |
| Selective reporting (reporting bias) | Low risk | All expected outcomes were reported |
| Other bias | Low risk | No other apparent sources of bias |